Schizophrenia

Question 1

When does schizophrenia typically start?

Answer 1

Adolescence or as a young adult

Question 2

What are examples of first rank symptoms?

Answer 2

• Delusion
• Auditory hallucination
• Thought disorder e.g. thought withdrawal
• Passivity phenomena e.g. ‘made’ feelings

Question 3

What is a delusion?

Answer 3

• Fixed rigidly held belief not understandable on the basis of a patient’s cultural background
• Typically dominates thinking and is socially disabling

Question 4

What are negative symptoms?

Answer 4

• Persistent loss of usual activities and interests, apathy, blunted emotional responses, speech reduction
• Social withdrawal, impaired attention, anhedonia, lethargy

Question 5

What is passivity phenomena?

Answer 5

• Patients belief that they no longer control their actions, feelings or thoughts
• External agent controlling them to act, feel or think

Question 6

What is presented in Whitford’s theory, which explains the symptoms of schizophrenia?

Answer 6

The concept of brain abnormalities and abnormal salience (hallucinations and delusions) and agency (passivity phenomena)

Question 7

What does Whitford’s theory suggest as the cause of schizophrenia?

Answer 7

• SZ arises because of some incompletely understood genetic trigger during late adolescence/early adulthood
• Myelin is structurally abnormal and consequently abnormal in ability to insulate axon membranes affecting velocity of axon potentials
• Functional disconnections result in disruption of corollary discharge mechanisms

Question 8

What is the risk of SZ in monozygotic twins or a child with both parents having SZ?

Answer 8

45% increased risk of having SZ

Question 9

What is the risk to children of SZ mothers adopted soon after birth by non-SZ families?

Answer 9

13% increased risk - no increased risk of developing SZ for children of non-SZ parents similarly adopted

Question 10

What is the problem with molecular genetic studies in SZ?

Answer 10

• They have not identified clinically useful findings for drug discovery nor does this seem likely
• There are multiple genes implicated in SZ each with very little effect

Question 11

Where are the biggest white matter abnormalities in the brains of SZ patients?

Answer 11

Corona radiata and corpus callosum

Question 12

What is corollary discharge?

Answer 12

• Efference copy of motor command is used to create a predicted sensory feedback (corollary discharge) which estimates the sensory consequences of a motor command
• Actual sensory feedback compared with predicted feedback informs the CNS about external actions
• This is how you know the difference between external world movement and self-generated eye movement

Question 13

How does abnormal corollary discharge relate to auditory hallucinations in SZ patients?

Answer 13

Auditory hallucinations are due to a failure of corollary discharge connections due to impaired white matter tract integrity from Broca’s area to superior temporal gyrus/Wernicke’s area so auditory hallucinations are untagged sub-vocal speech therefore not recognised by the brain as self-generated

Question 14

What is the altered sense of agency in SZ thought to be due to?

Answer 14

Dysfunction of perception and action therefore faulty integration of prior knowledge and expectations with evidence

Question 15

What are the 2 separate cues to sense of agency?

Answer 15

• Sensorimotor system and cognitive system
• The widely held view currently - physiological prediction deficit in sensorimotor function leads to distorted agency cues

Question 16

What are the 2 ways in which linkage of action and effect are generated?

Answer 16

• Predicatively (action predicted to generate a given effect) - corollary discharge
• Retrospectively (inference action caused effect) - cognitive mechanism

Question 17

In terms of predictive and retrospective components of intentional binding, what do SZ patients lack?

Answer 17

• Absent predictive component with strong retrospective component
• Higher incidence of first rank symptoms, such as delusions and hallucinations, associated with more reduced predictive component

Question 18

What is the key mechanism underlying the sense of agency?

Answer 18

Association between ones action and external effect

Question 19

What did the Moore et al (2012) review show about the prediction component of intentional binding?

Answer 19

Patients were generating imprecise prediction rather than no predictions

Question 20

Why could hyperdopaminergia occur in SZ?

Answer 20

If the brain’s response to constantly experiencing internally generated events as unexpected external events is to increase dopamine firing then hyperdopaminergia results

Question 21

The mesolimbic DA system is a critical component of the attribution of salience. Describe the process of salience

Answer 21

This is the process by which events and thought grab attention and influence goal-directed behaviour because of association with reward or punishment, linked to concepts of value

Question 22

How is salience related to delusions and auditory hallucinations?

Answer 22

• Delusions - belief with extremely high abnormal salience
• Auditory hallucinations - abnormally high salience of internal thoughts

Question 23

How does DA affect salience?

Answer 23

In health, DA mediates the process of salience acquisition and expression but does not create the process (DA release is dependent on external stimuli)

Question 24

What happens to DA release and thus salience in psychosis?

Answer 24

• There is dysregulated DA transmission leading to stimulus independent release of DA
• This leads to creation of abnormal saliences (psychotic symptoms)

Question 25

What property do all anti-psychotics have in common?

Answer 25

They dampen salience acquisition

Question 26

How was dampening of salience by anti-psychotics demonstrated in behavioural studies in rats in the 1950s?

Answer 26

• Rats had a punishment avoidance schedule - associated bell with an electric shock, so would try to avoid
• Rats + anti-psychotics - function not impaired and still responding to shock but there is a forgetfulness of motive i.e. reduced salience

Question 27

What pathways are punishment avoidance and reward-learning associated with respectively?

Answer 27

• Indirect basal ganglia pathway and D2 receptors
• Reward learning is associated with direct basal ganglia pathway and D1 receptors

Question 28

What property do anti-psychotics need to have to be clinically effective?

Answer 28

They need to block D2 receptors (indirect basal ganglia pathway)

Question 29

Name some examples of typical anti-psychotics

Answer 29

Chlorpomazine, haloperidol

Question 30

Name some examples of atypical anti-psychotics

Answer 30

Clozapine, olanzapine, risperidone, quetiapine

Question 31

Why are regular blood counts needed for patients on clozapine?

Answer 31

Risk of agranulocytosis

Question 32

What are some clinical factors of SZ associated with a good prognosis?

Answer 32

• Female, abrupt onset, married, good pre-morbid social adjustment, short duration of illness, lack of negative symptoms, lack of cognitive impairment, no ventricular enlargement
• Bold = if present tend to indicate poor prognosis

Question 33

10% of SZ patients commit suicide. What factors makes this more likely?

Answer 33

Early in illness, males with chronic illness, unemployed, tardive dyskinesia, previous high educational attainment, sudden stoppage of medication, recent discharge from hospital

Question 34

Grey matter abnormalities occur early in SZ. Why are these abnormalities thought to occur?

Answer 34

• Due to neuropil elimination not neuronal death
• Most likely loss of dendritic arbors and associated synaptic infrastructure

Question 35

What areas of the brain have been shown to atrophy in SZ?

Answer 35

Smaller hippocampus, amygdala, thalamus, nucleus accumbens